Molecular Analysis of the Complete Genome of a Simian Foamy Virus Infecting Hylobates pileatus (pileated gibbon) Reveals Ancient Co-Evolution with Lesser Apes

Foamy viruses (FVs) are complex retroviruses present in many mammals, including nonhuman primates, where they are called simian foamy viruses (SFVs). SFVs can zoonotically infect humans, but very few complete SFV genomes are available, hampering the design of diagnostic assays. Gibbons are lesser apes widespread across Southeast Asia that can be infected with SFV, but only two partial SFV sequences are currently available. We used a metagenomics approach with next-generation sequencing of nucleic acid extracted from the cell culture of a blood specimen from a lesser ape, the pileated gibbon (Hylobates pileatus), to obtain the complete SFVhpi_SAM106 genome. We used Bayesian analysis to co-infer phylogenetic relationships and divergence dates. SFVhpi_SAM106 is ancestral to other ape SFVs with a divergence date of ~20.6 million years ago, reflecting ancient co-evolution of the host and SFVhpi_SAM106. Analysis of the complete SFVhpi_SAM106 genome shows that it has the same genetic architecture as other SFVs but has the longest recorded genome (13,885-nt) due to a longer long terminal repeat region (2,071 bp). The complete sequence of the SFVhpi_SAM106 genome fills an important knowledge gap in SFV genetics and will facilitate future studies of FV infection, transmission, and evolutionary history.

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Simian Foamy Virus Co-Infections

Viruses ◽

10.3390/v11100902 ◽

2019 ◽

Vol 11 (10) ◽

pp. 902 ◽

Cited By ~ 1

Author(s):

Shannon M. Murray ◽

Maxine L. Linial

Keyword(s):

Nonhuman Primate ◽

Human Disease ◽

Nonhuman Primates ◽

Foamy Virus ◽

Natural Populations ◽

Simian Foamy Virus ◽

Immunodeficiency Virus ◽

Foamy Viruses ◽

Natural Hosts ◽

Research Facilities

Foamy viruses (FVs), also known as spumaretroviruses, are complex retroviruses that are seemingly nonpathogenic in natural hosts. In natural hosts, which include felines, bovines, and nonhuman primates (NHPs), a large percentage of adults are infected with FVs. For this reason, the effect of FVs on infections with other viruses (co-infections) cannot be easily studied in natural populations. Most of what is known about interactions between FVs and other viruses is based on studies of NHPs in artificial settings such as research facilities. In these settings, there is some indication that FVs can exacerbate infections with lentiviruses such as simian immunodeficiency virus (SIV). Nonhuman primate (NHP) simian FVs (SFVs) have been shown to infect people without any apparent pathogenicity. Humans zoonotically infected with simian foamy virus (SFV) are often co-infected with other viruses. Thus, it is important to know whether SFV co-infections affect human disease.

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Structural and Evolutionary Analysis of an Orangutan Foamy Virus

Journal of Virology ◽

10.1128/jvi.77.15.8584-8587.2003 ◽

2003 ◽

Vol 77 (15) ◽

pp. 8584-8587 ◽

Cited By ~ 10

Author(s):

Ernst J. Verschoor ◽

Susan Langenhuijzen ◽

Saskia van den Engel ◽

Henk Niphuis ◽

Kristin S. Warren ◽

...

Keyword(s):

Foamy Virus ◽

Its Sequence ◽

Old World Monkeys ◽

Evolutionary Analysis ◽

Proviral Genome ◽

Simian Foamy Virus ◽

Long Period ◽

Bornean Orangutan ◽

Foamy Viruses ◽

Virus Genomes

ABSTRACT The full-length proviral genome of a foamy virus infecting a Bornean orangutan was amplified, and its sequence was analyzed. Although the genome showed a clear resemblance to other published foamy virus genomes from apes and monkeys, phylogenetic analysis revealed that simian foamy virus SFVora was evolutionarily equidistant from foamy viruses from other hominoids and from those from Old World monkeys. This finding suggests an independent evolution within its host over a long period of time.

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First Complete Genome Sequence of a Simian Foamy Virus Isolate from a Cynomolgus Macaque

Genome Announcements ◽

10.1128/genomea.01332-16 ◽

2016 ◽

Vol 4 (6) ◽

Cited By ~ 1

Author(s):

Koji Sakai ◽

Yasushi Ami ◽

Yuriko Suzaki ◽

Tetsuro Matano

Keyword(s):

Genome Sequence ◽

Macaca Fascicularis ◽

Virus Isolate ◽

Foamy Virus ◽

Cynomolgus Macaque ◽

Open Reading Frames ◽

Proviral Genome ◽

Simian Foamy Virus ◽

Foamy Viruses ◽

Reading Frames

We report here the first complete proviral genome sequence (DDBJ/ENA/GenBank accession no. LC094267) of a simian foamy virus, SFVmfa/Cy5061, isolated from a cynomolgus macaque ( Macaca fascicularis ). This proviral genome consists of 12,965 nucleotides and has five open reading frames, gag , pol , env , tas , and bet , as with other foamy viruses.

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Interspecies Transmission of Simian Foamy Virus in a Natural Predator-Prey System

Journal of Virology ◽

10.1128/jvi.00549-08 ◽

2008 ◽

Vol 82 (15) ◽

pp. 7741-7744 ◽

Cited By ~ 49

Author(s):

Fabian H. Leendertz ◽

Florian Zirkel ◽

Emmanuel Couacy-Hymann ◽

Heinz Ellerbrok ◽

Vladimir A. Morozov ◽

...

Keyword(s):

Foamy Virus ◽

Interspecies Transmission ◽

Primate Species ◽

Simian Foamy Virus ◽

Predator Prey ◽

Prey System ◽

Colobus Monkeys ◽

Foamy Viruses ◽

Natural Predator ◽

Species Specific

ABSTRACT Simian foamy viruses (SFV) are ancient retroviruses of primates and have coevolved with their host species for as many as 30 million years. Although humans are not naturally infected with foamy virus, infection is occasionally acquired through interspecies transmission from nonhuman primates. We show that interspecies transmissions occur in a natural hunter-prey system, i.e., between wild chimpanzees and colobus monkeys, both of which harbor their own species-specific strains of SFV. Chimpanzees infected with chimpanzee SFV strains were shown to be coinfected with SFV from colobus monkeys, indicating that apes are susceptible to SFV superinfection, including highly divergent strains from other primate species.

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A Seminomadic Population in Bangladesh with Extensive Exposure to Macaques Does Not Exhibit High Levels of Zoonotic Simian Foamy Virus Infection

Journal of Virology ◽

10.1128/jvi.01065-15 ◽

2015 ◽

Vol 89 (14) ◽

pp. 7414-7416 ◽

Cited By ~ 5

Author(s):

Karen L. Craig ◽

M. Kamrul Hasan ◽

Dana L. Jackson ◽

Gregory A. Engel ◽

Khanh Soliven ◽

...

Keyword(s):

Virus Infection ◽

Ethnic Group ◽

Infection Rate ◽

Nonhuman Primates ◽

Foamy Virus ◽

Pcr Assay ◽

Simian Foamy Virus ◽

Foamy Viruses

Simian foamy viruses (SVF) are ubiquitous in nonhuman primates (NHP). SFV can be zoonotically transmitted to humans who either work with or live commensally with NHP. We analyzed the blood of 45 Bangladeshi performing monkey owners (an ethnic group called the Bedey) for SFV infection. Surprisingly, a PCR assay failed to detect SFV infection in any of these participants. This is in contrast to our previously reported infection rate of about 5% among Bangladeshi villagers.

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Packaging Cell Lines for Simian Foamy Virus Type 1 Vectors

Journal of Virology ◽

10.1128/jvi.73.5.4498-4501.1999 ◽

1999 ◽

Vol 73 (5) ◽

pp. 4498-4501 ◽

Cited By ~ 16

Author(s):

Min Wu ◽

Ayalew Mergia

Keyword(s):

Cell Line ◽

Cell Lines ◽

Virus Type ◽

Foamy Virus ◽

Vector System ◽

Simian Foamy Virus ◽

Packaging Cell Line ◽

Packaging Cell ◽

Foamy Viruses

ABSTRACT Foamy viruses are nonpathogenic retroviruses that offer several unique opportunities for gene transfer in various cell types from different species. We have previously demonstrated the utility of simian foamy virus type 1 (SFV-1) as a vector system by transient expression assay (M. Wu et al., J. Virol. 72:3451–3454, 1998). In this report, we describe the first stable packaging cell lines for foamy virus vectors based on SFV-1. We developed two packaging cell lines in which the helper DNA is placed under the control of either a constitutive cytomegalovirus (CMV) immediate-early gene or inducible tetracycline promoter for expression. Although the constitutive packaging expressing cell line had a higher copy number of packaging DNA, the inducible packaging cell line produced four times more vector particles. This result suggested that the structural gene products in the constitutively expressing packaging cell line were expressed at a level that is not toxic to the cells, and thus vector production was reduced. The SFV-1 vector in the presence of vesicular stomatitis virus envelope protein G (VSV-G) produced an insignificant level of transduction, indicating that foamy viruses could not be pseudotyped with VSV-G to generate high-titer vectors. The availability of stable packaging cell lines represents a step toward the use of an SFV-1 vector delivery system that will allow scaled-up production of vector stocks for gene therapy.

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Contemporary Distribution, Estimated Age, and Prehistoric Migrations of Old World Monkey Retroviruses

Epidemiologia ◽

10.3390/epidemiologia2010005 ◽

2021 ◽

Vol 2 (1) ◽

pp. 46-67

Author(s):

Antoinette C. van der Kuyl

Keyword(s):

Close Contact ◽

World Monkey ◽

Foamy Virus ◽

Endogenous Retrovirus ◽

Papio Cynocephalus ◽

Endogenous Virus ◽

Simian Foamy Virus ◽

Old World ◽

T Lymphotropic Virus ◽

Type D

Old World monkeys (OWM), simians inhabiting Africa and Asia, are currently affected by at least four infectious retroviruses, namely, simian foamy virus (SFV), simian immunodeficiency virus (SIV), simian T-lymphotropic virus (STLV), and simian type D retrovirus (SRV). OWM also show chromosomal evidence of having been infected in the past with four more retroviral species, baboon endogenous virus (BaEV), Papio cynocephalus endogenous virus (PcEV), simian endogenous retrovirus (SERV), and Rhesus endogenous retrovirus-K (RhERV-K/SERV-K1). For some of the viruses, transmission to other primates still occurs, resulting, for instance, in the HIV pandemic. Retroviruses are intimately connected with their host as they are normally spread by close contact. In this review, an attempt to reconstruct the distribution and history of OWM retroviruses will be made. A literature overview of the species infected by any of the eight retroviruses as well as an age estimation of the pathogens will be given. In addition, primate genomes from databases have been re-analyzed for the presence of endogenous retrovirus integrations. Results suggest that some of the oldest retroviruses, SERV and PcEV, have travelled with their hosts to Asia during the Miocene, when a higher global temperature allowed simian expansions. In contrast, younger viruses, such as SIV and SRV, probably due to the lack of a primate continuum between the continents in later times, have been restricted to Africa and Asia, respectively.

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Generation of an improved foamy virus vector by dissection of cis-acting sequences

Journal of General Virology ◽

10.1099/vir.0.006312-0 ◽

2009 ◽

Vol 90 (2) ◽

pp. 481-487 ◽

Cited By ~ 18

Author(s):

Tatiana Wiktorowicz ◽

Katrin Peters ◽

Nicole Armbruster ◽

Andre F. Steinert ◽

Axel Rethwilm

Keyword(s):

Foamy Virus ◽

Human Mesenchymal Stem Cells ◽

Viral Capsid ◽

Rna Packaging ◽

Gag Protein ◽

Protein Precursor ◽

Cis Acting ◽

Foamy Viruses ◽

Protein Incorporation ◽

Primary Human Cells

In contrast to other retroviruses, foamy viruses (FVs) generate their Pol protein precursor independently of the Gag protein from a spliced mRNA. The exact mechanism of Pol protein incorporation into the viral capsid is poorly understood. Previously, we showed that Pol encapsidation critically depends on the packaging of (pre-) genomic RNA and identified two distinct signals within the cis-acting sequences (CASI and CASII), Pol encapsidation sequences (PESI and PESII), which are required for Pol capsid incorporation. Here, we investigated whether the presence of PESI and PESII in an FV vector is sufficient for Pol encapsidation and whether the rather extended CASII element can be shortened without loss of functionality. Our results indicate that (i) the presence of PESI and II are not sufficient for Pol encapsidation, (ii) prototype FV vectors with a shortened CASII element retain Pol incorporation and full functionality, in particular upon transducing fibroblasts and primary human mesenchymal stem cells, (iii) the presence of the central poly purine tract significantly increased the transduction rates of FV vectors and (iv) Pol encapsidation and RNA packaging can be clearly separated. In essence, we designed a new FV vector that bears approximately 850 bp less of CAS than previously established vectors and is fully functional when analysed to transduce cell lines and primary human cells.

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RNA and Protein Requirements for Incorporation of the Pol Protein into Foamy Virus Particles

Journal of Virology ◽

10.1128/jvi.79.11.7005-7013.2005 ◽

2005 ◽

Vol 79 (11) ◽

pp. 7005-7013 ◽

Cited By ~ 35

Author(s):

Katrin Peters ◽

Tatiana Wiktorowicz ◽

Martin Heinkelein ◽

Axel Rethwilm

Keyword(s):

Foamy Virus ◽

Genomic Rna ◽

Rna Packaging ◽

Gag Protein ◽

Protein Precursor ◽

Protein Requirements ◽

Virus Particles ◽

Foamy Viruses ◽

Protein Incorporation ◽

The Individual

ABSTRACT Foamy viruses (FVs) generate their Pol protein precursor molecule independently of the Gag protein from a spliced mRNA. This mode of expression raises the question of the mechanism of Pol protein incorporation into the viral particle (capsid). We previously showed that the packaging of (pre)genomic RNA is essential for Pol encapsidation (M. Heinkelein, C. Leurs, M. Rammling, K. Peters, H. Hanenberg, and A. Rethwilm, J. Virol. 76:10069-10073, 2002). Here, we demonstrate that distinct sequences in the RNA, which we termed Pol encapsidation sequences (PES), are required to incorporate Pol protein into the FV capsid. Two PES were found, which are contained in the previously identified cis-acting sequences necessary to transfer an FV vector. One PES is located in the U5 region of the 5′ long terminal repeat and one at the 3′ end of the pol gene region. Neither element has any significant effect on RNA packaging. However, deletion of either PES resulted in a significant reduction in Pol encapsidation. On the protein level, we show that only the Pol precursor, but not the individual reverse transcriptase (RT) and integrase (IN) subunits, is incorporated into FV particles. However, enzymatic activities of the protease (PR), RT, or IN are not required. Our results strengthen the view that in FVs, (pre)genomic RNA functions as a bridging molecule between Gag and Pol precursor proteins.

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